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| | ==Structure of Calcineurin in complex with NFATc1 LxVP peptide== | | ==Structure of Calcineurin in complex with NFATc1 LxVP peptide== |
| - | <StructureSection load='5sve' size='340' side='right' caption='[[5sve]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='5sve' size='340' side='right'caption='[[5sve]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5sve]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SVE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SVE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5sve]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SVE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.596Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5sve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sve OCA], [http://pdbe.org/5sve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sve RCSB], [http://www.ebi.ac.uk/pdbsum/5sve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sve ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5sve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sve OCA], [https://pdbe.org/5sve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sve RCSB], [https://www.ebi.ac.uk/pdbsum/5sve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sve ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PP2BA_HUMAN PP2BA_HUMAN]] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.<ref>PMID:15671020</ref> <ref>PMID:18838687</ref> [[http://www.uniprot.org/uniprot/CANB1_HUMAN CANB1_HUMAN]] Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity. | + | [https://www.uniprot.org/uniprot/PP2BA_HUMAN PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.<ref>PMID:15671020</ref> <ref>PMID:18838687</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Calcineurin|Calcineurin]] | + | *[[Calcineurin 3D structures|Calcineurin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Page, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Peti, W]] | + | [[Category: Page R]] |
| - | [[Category: Sheftic, S R]]
| + | [[Category: Peti W]] |
| - | [[Category: Hydrolase]] | + | [[Category: Sheftic SR]] |
| - | [[Category: Protein binding]] | + | |
| Structural highlights
Function
PP2BA_HUMAN Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.[1] [2]
Publication Abstract from PubMed
Ser/thr phosphorylation is the primary reversible covalent modification of proteins in eukaryotes. As a consequence, it is the reciprocal actions of kinases and phosphatases that act as key molecular switches to fine tune cellular events. It has been well documented that ~400 human ser/thr kinases engage substrates via consensus phosphosite sequences. Strikingly, we know comparatively little about the mechanism by which ~40 human protein ser/thr phosphatases (PSPs) dephosphorylate ~15000 different substrates with high specificity. The identification of substrates of the essential PSP calcineurin (CN) has been exceptionally challenging and only a small fraction has been biochemically confirmed. It is now emerging that CN binds regulators and substrates via two short linear motifs (SLiMs), the well-studied PxIxIT SLiM and the LxVP SLiM, which remains controversial at the molecular level. Here we describe the crystal structure of CN in complex with its substrate NFATc1 and show that the LxVP SLiM is correctly defined as piLxVP. Bioinformatics studies using the piLxVP SLiM resulted in the identification of 567 potential CN substrates; a small subset was experimentally confirmed. This combined structural-bioinformatics approach provides a powerful method for dissecting the CN interaction network and for elucidating the role of CN in human health and disease.
Investigating the human Calcineurin Interaction Network using the piLxVP SLiM.,Sheftic SR, Page R, Peti W Sci Rep. 2016 Dec 15;6:38920. doi: 10.1038/srep38920. PMID:27974827[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang Y, Shibasaki F, Mizuno K. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin. J Biol Chem. 2005 Apr 1;280(13):12683-9. Epub 2005 Jan 24. PMID:15671020 doi:M411494200
- ↑ Cereghetti GM, Stangherlin A, Martins de Brito O, Chang CR, Blackstone C, Bernardi P, Scorrano L. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15803-8. doi:, 10.1073/pnas.0808249105. Epub 2008 Oct 6. PMID:18838687 doi:10.1073/pnas.0808249105
- ↑ Sheftic SR, Page R, Peti W. Investigating the human Calcineurin Interaction Network using the piLxVP SLiM. Sci Rep. 2016 Dec 15;6:38920. doi: 10.1038/srep38920. PMID:27974827 doi:http://dx.doi.org/10.1038/srep38920
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